Septic shock is a condition which may be associated with Gram positive infections, such as those due to pneumococci and streptococci, or with Gram negative infections, such as those due to Escherichia coli, Klebsiella-Enterobacter, Pseudomonas, and Serratia. In the case of the Gram-negative organisms the shock syndrome is not due to bloodstream invasion with bacteria per se but is related to release of endotoxin, the lipopolysaccharide (LPS) moiety of the organisims' cell walls, into the circulation.
Septic shock is characterized by inadequate tissue perfusion and circulatory insufficiency due to diffuse cell and tissue injury and the pooling of blood in the microcirculation. Hypotension, oliguria, tachycardia, tachypnea and fever are observed in most patients.
The mortality rate associated with septic shock from gram negative bacteremia remains unacceptably high despite the availability of a wide variety of potent antimicrobial agents. The failure of antimicrobial agents to improve the outlook in septic shock is related to large part to the intrinsic toxicity of endotoxin (LPS) produced by gram negative bacteria. Antibiotics have no immediate effect on endotoxin and may transiently elevate circulating endotoxin levels following the initiation of therapy during Gram negative bacteremia.
Alternative measures have been sought to prevent the deleterious effects of endotoxemia. An attractive strategy has been the development of active or passive immunotherapy against endotoxin itself. Serotype specific immunity to LPS and polyclonal and monoclonal antibody immunotherapy directed against the core glycolipid of gram negative bacterial LPS have been at least partially successful in a number of experimental and clinical studies of septic shock.
Recent evidence indicated that the monocyte/macrophage derived cytokine, tumour necrosis factor-alpha, is a principal mediator of the hemodynamic and pathophysiologic effects of endotoxin. Polyclonal and monoclonal antibodies directed against tumor necrosis factor have demonstrated protective efficacy against potentially lethal doses of endotoxin as well as large intravenous doses of Escherichia coli.